Maternal Dietary Vitamin D Intake during Pregnancy Is Associated with Allergic Disease Symptoms in Children at 3 Years Old: The Japan Environment and Children's Study.

INTRODUCTION: Vitamin D plays an important role in the immune system, and postnatal vitamin D insufficiency is one of the risk factors for the development of allergic disease. However, the effects of women's vitamin D intake during pregnancy on the prevalence of allergic disease in their children remain controversial. METHODS: From the Japan Environment and Children's Study, an ongoing nationwide birth cohort study, we obtained information on maternal dietary vitamin D intake determined using a food frequency questionnaire and parent-reported allergic disease symptoms based on the ISAAC questionnaire in children at 3 years of age. RESULTS: From the full dataset of 103,060 pregnancies, we analyzed complete data for 73,309 mother-child pairs. The prevalence of current wheeze, current rhinitis, current rhino-conjunctivitis, current eczema, ever asthma, ever pollinosis, and ever atopic dermatitis in the children was 17.2%, 29.7%, 3.8%, 15.2%, 9.6%, 3.7%, and 11.0%, respectively. The ORs for current rhinitis were significantly lower in the 3rd, 4th, and 5th quintiles than in the 1st quintile after adjustment for various covariates and showed a linear association. The ORs for ever pollinosis were significantly lower in the 2nd, 3rd, and 4th quintiles than in the 1st quintile, showing a U-shaped curve. There was no clear association between mothers' dietary vitamin D intake and symptoms of asthma or atopic dermatitis in their 3-year-old children. CONCLUSION: Maternal dietary vitamin D intake during pregnancy is associated with the ORs for nasal allergies in children at the age of 3 years. Further studies are warranted to evaluate the appropriate intake dose of vitamin D for pregnant women to prevent the development of nasal allergies in their children.

Season of birth and atopic dermatitis in early infancy: results from the Japan Environment and Children's Study.

BACKGROUND: Atopic dermatitis (AD) is reported to be more prevalent in children who were born in autumn than in spring. Here, we investigated how early the association between season of birth and eczema or AD can be observed in the postnatal period. We also examined whether specific prevalence outcomes for infant eczema and AD differed according to sex and maternal history of allergic disease in a large Japanese cohort. METHODS: Using data of 81,615 infants from the Japan Environment and Children's Study, we examined the associations of birth month or season with four different outcomes-eczema at 1 month, 6 months, and 1 year of age and physician-diagnosed AD up to 1 year of age-using multiple logistic regression analysis. We also analyzed the effect of maternal history of allergic disease on these outcomes stratified by infant sex. RESULTS: The risk of eczema at 1 month was highest in infants born in July. In contrast, infants born in autumn had higher risks of eczema at 6 months (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 2.10-2.30) and at 1 year (aOR, 1.08; 95% CI, 1.02-1.14) and of physician-diagnosed AD up to 1 year of age (aOR, 1.33; 95% CI, 1.20-1.47) compared with infants born in spring. Eczema and AD were more prevalent in infants with a maternal history of allergic disease, particularly boys. CONCLUSIONS: Our findings suggest that the prevalence of AD is associated with the season of observation. Eczema is prevalent in infants born in autumn, and this phenomenon was observed in infants as young as 6 months old. The risk associated with being born in autumn was particularly clear in boys with a maternal history of allergic disease. TRIAL REGISTRATION: UMIN000030786.

Maternal exposure to smoking and infant's wheeze and asthma: Japan Environment and Children's Study.

BACKGROUND: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. METHODS: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. RESULTS: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1-10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270-1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341-2.078; asthma: 1-10 cigarettes/day: aOR 1.389, 95% CI 1.087-1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045-2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083-1.256; asthma: aOR 1.258, 95% CI 1.075-1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739-2.317; asthma: aOR 1.995, 95% CI 1.528-2.605). CONCLUSIONS: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.

[A CASE OF VOCAL CORD DYSFUNCTION, WHO USED ADRENALIN AUTOINJECTOR (EPIPEN®) FREQUENTLY AFTER BEING DIAGNOSED AS ANAPHYLAXIS].

We experienced a case of vocal cord dysfunction (VCD) in a child to whom an adrenaline autoinjector (Epipen®) had been prescribed and frequently used following a diagnosis of exercise-induced anaphylaxis. An exercise test was performed to investigate her frequent episodes of anaphylaxis-like symptoms. A few minutes after starting the test, signs of dyspnea, such as throat tightness and stridor, appeared, although hypoxia was not present and her respiratory sounds were normal. Medications were not effective for treating her respiratory symptoms. Laryngoscopy performed at the test revealed bizarre vocal cord movement, which was diagnosed as VCD. The symptoms gradually diminished after the initiation of biofeedback therapy, including pursed lips breathing and abdominal breathing. Thereafter, she did not use an adrenaline autoinjector when symptoms appeared; instead, she would perform biofeedback therapy before using the adrenaline autoinjector. Thus, VCD should be included in the differential diagnosis of patients who show anaphylactic symptoms that are resistant to preventive therapy.

[A PEDIATRIC CASE OF DIFFUSE PANBRONCHIOLITIS WHO PREDOMINANTLY SHOWED RESTRICTIVE PULMONARY DYSFUNCTION AND DRAMATICALLY RESPONDED TO MACROLIDE LOW-DOSE LONG-TERM THERAPY.]

A 12-year-old boy visited our hospital with complaints of chronic cough and dyspnea. Chest X-ray and CT revealed diffuse granular shadow in the bilateral lung fields and "Tree-in-bud appearance" in the peripheral airways, respectively. Sinusitis was present, and restrictive disorder was predominantly found in pulmonary function. The patient was diagnosed with DPB, and long-term therapy was started with low-dose clarithromycin (CAM), The patient showed a dramatic response to CAM, with improvements of both the clinical symptoms and pulmonary function within 1-2 months. According to the relevant literature, in adult patients with this disease, pulmonary dysfunction starts from an obstructive pattern; however, this is not the case in pediatric patients. It was therefore suggested that the mechanisms underlying the development of pulmonary dysfunction in cases of childhood onset differs from those with an adult onset.

The impact of exposure to desert dust on infants' symptoms and countermeasures to reduce the effects.

BACKGROUND: The association between particulate matter (PM), including desert dust, and allergic symptoms has not been well studied. We examined whether PM exacerbated nose/eye/respiratory symptoms in infants, with a focus on the desert dust element, and assessed possible countermeasures. METHODS: We conducted a panel study of 1492 infants from October 2014 to July 2016 in 3 regions in Japan as an adjunct study of the Japan Environment and Children's Study. Infants' daily symptom scores and behaviors were acquired by web-based questionnaires sent to mothers, who answered within a day using mobile phones. Odds ratios (OR) for symptom development per increased fine PM or desert dust exposure were estimated. Regular use of medications and behaviors on the day of exposure were investigated as possible effect modifiers. RESULTS: Infants developed nose/eye/respiratory symptoms significantly more often in accordance with fine particulate levels (adjusted OR per 10 µg/m3 increase: 1.04, 95% confidence interval [CI]: 1.01-1.07). A model including both fine particulates and desert dust showed reduced OR for fine particulates and robust OR for desert dust (adjusted OR per 0.1/km increase: 1.16, 95% CI: 1.09-1.23). An increased OR was observed both in infants who had previously wheezed and in those who had never wheezed. Receiving information on the particulate forecast, reducing time outdoors, closing windows, and regular use of leukotriene receptor antagonists were significant effect modifiers. CONCLUSIONS: Transborder desert dust arrival increased the risk of nose/eye/respiratory symptoms development in infants. Regular use of leukotriene receptor antagonists and other countermeasures reduced the risk.

The severity of reaction after food challenges depends on the indication: A prospective multicenter study.

BACKGROUND: There are expanding indications for oral food challenges (OFCs). Although several studies have examined the risk of OFCs, little has been reported on allergic reactions during OFCs depending on the indication. This study assessed the prevalence, severity, and treatment of allergic reactions depending on the indication for OFCs. METHODS: We performed a prospective multicenter study between March 2012 and May 2013. Severity of symptoms elicited by OFCs was classified according to grading of anaphylaxis that ranges from grade 1 (most mild) to grade 5 (most severe). RESULTS: A total of 5062 cases (median age, 3.8 years; males, 65.2%) were analyzed. Allergic reactions were elicited in 2258 (44.6%) OFCs, of which 991 (43.9%) were classified as grade 1, 736 (32.6%) were classified as grade 2, 340 (15.1%) were classified as grade 3, and 191 (8.5%) were classified as grade 4-5. Epinephrine was administered in 7.1% (n = 160) of positive OFCs. Among the top three most common food allergens (hen's egg, cow's milk, and wheat), severity differed significantly depending on the indication for OFC, and adjusted standardized residuals indicated that severity of allergic reactions was higher for the indication to assess threshold level for oral immunotherapy. In addition, the prevalence of epinephrine use was highest for the indication to determine safe intake quantity. CONCLUSIONS: Our study suggested that prevalence, severity, and treatment of allergic reactions differ depending on the indication for OFC. Further studies are needed to determine differences in risks depending on the indication for OFC.

Excision release of 5?hydroxycytosine oxidatively induced DNA base lesions from the lung genome by cat dander extract challenge stimulates allergic airway inflammation.

BACKGROUND: Ragweed pollen extract (RWPE) induces TLR4-NFκB-CXCL-dependent recruitment of ROS-generating neutrophils to the airway and OGG1 DNA glycosylase-dependent excision of oxidatively induced 8-OH-Gua DNA base lesions from the airway epithelial cell genome. Administration of free 8-OH-Gua base stimulates RWPE-induced allergic lung inflammation. These studies suggest that stimulation of innate receptors and their adaptor by allergenic extracts initiates excision of a set of DNA base lesions that facilitate innate/allergic lung inflammation. OBJECTIVE: To test the hypothesis that stimulation of a conserved innate receptor/adaptor pathway by allergenic extracts induces excision of a set of pro-inflammatory oxidatively induced DNA base lesions from the lung genome that stimulate allergic airway inflammation. METHODS: Wild-type (WT), Tlr4KO, Tlr2KO, Myd88KO, and TrifKO mice were intranasally challenged once or repeatedly with cat dander extract (CDE), and innate or allergic inflammation and gene expression were quantified. We utilized GC-MS/MS to quantify a set of oxidatively induced DNA base lesions after challenge of naïve mice with CDE. RESULTS: A single CDE challenge stimulated innate neutrophil recruitment that was partially dependent on TLR4 and TLR2, and completely on Myd88, but not TRIF. A single CDE challenge stimulated MyD88-dependent excision of DNA base lesions 5-OH-Cyt, FapyAde, and FapyGua from the lung genome. A single challenge of naïve WT mice with 5-OH-Cyt stimulated neutrophilic lung inflammation. Multiple CDE instillations stimulated MyD88-dependent allergic airway inflammation. Multiple administrations of 5-OH-Cyt with CDE stimulated allergic sensitization and allergic airway inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: We show for the first time that CDE challenge stimulates MyD88-dependent excision of DNA base lesions. Our data suggest that the resultant-free base(s) contribute to CDE-induced innate/allergic lung inflammation. We suggest that blocking the MyD88 pathway in the airways with specific inhibitors may be a novel targeted strategy of inhibiting amplification of innate and adaptive immune inflammation in allergic diseases by oxidatively induced DNA base lesions.

Childhood asthma control in Japan: A nationwide, cross-sectional, web-based survey.

BACKGROUND: Recent surveys have shown that many patients with asthma experience uncontrolled symptoms and decreased quality of life due to their disease. However, few large population-based studies have evaluated asthma control in Japanese children. OBJECTIVE: To show the reality of asthma control and the pattern of asthma controller medication use among Japanese children. METHODS: In 2012, a web-based survey was conducted to identify children aged 6 to 11 years with asthma in Japan. Among children with current asthma, we collected information regarding their asthma controller medication use and evaluated the control level of asthma using the Childhood Asthma Control Test (C-ACT). In this study, a C-ACT score of 19 or less, 20 to 22 and over 22 were classified as uncontrolled asthma, well-controlled asthma, and optimally controlled asthma, respectively. RESULTS: Among the 3,033 children with current asthma, 442 (14.6%), 635 (20.9%), and 1,956 (64.5%) children had uncontrolled, well-controlled, and optimally controlled disease, respectively. In the past 1 month, 1,387 (45.7%) reported receiving at least 1 asthma controller medication with 638 (21.0%) reported receiving inhaled corticosteroid. Among the children with uncontrolled asthma, 67 (15.2%) were not receiving any asthma controller mediations. Among children receiving asthma controller medication, 27.0%, 31.4% and 41.5% had uncontrolled, well-controlled, and optimally controlled asthma, respectively. CONCLUSIONS: Although more than half of children with current asthma had optimally controlled disease, some children without any controller medications and more than a quarter of the children receiving asthma controller medications had uncontrolled disease.

Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation.

BACKGROUND: The National Health and Nutrition Examination Survey identified several pollens and cat dander as among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein 2 (MD2) is a TLR4 coreceptor, but its role in pollen- and cat dander-induced innate and allergic inflammation has not been critically evaluated. OBJECTIVE: We sought to elucidate the role of MD2 in inducing pollen- and cat dander-induced innate and allergic airway inflammation. METHODS: TCM(Null) (TLR4(Null), CD14(Null), MD2(Null)), TLR4(Hi), and TCM(Hi) cells and human bronchial epithelial cells with small interfering RNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of nuclear factor κB (NF-κB), secretion of the NF-κB-dependent CXCL8, or both were quantified. Wild-type mice or mice with small interfering RNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation was quantified. RESULTS: RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut, and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent and CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation. CONCLUSIONS: MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.

Effect of desert dust exposure on allergic symptoms: A natural experiment in Japan.

BACKGROUND: Desert dust originating from arid and semiarid areas is transported to widespread regions, including Japan. Desert dust particles exert adjuvant effects in animals. OBJECTIVE: To examine whether desert dust enhances allergic symptoms in real-life settings and to explore its effect modifiers. METHODS: We conducted an observational study of 3,327 pregnant women during spring and fall in October 2011 to May 2013 in 3 regions in Japan as an adjunct study of the Japan Environment & Children's Study. We acquired participants' daily symptom scores by sending a questionnaire to their mobile phones on high desert-dust days (>0.07/km) and on some randomly selected other days (control days) for each participant. RESULTS: Pregnant women had an increased risk of allergic symptoms on high desert-dust days (adjusted odds ratio [OR], 1.10; 95% CI, 1.04-1.18). The increased OR was mostly driven by those who showed positive IgE to Japanese cedar pollen when pollen simultaneously dispersed (adjusted OR, 1.25; 95% CI, 1.13-1.38), whereas no clear risk increase was observed in the absence of pollen or for participants with negative IgE to Japanese cedar pollen. The risk elevation was observed from low levels of desert dust in a dose-dependent manner even on control days. CONCLUSION: Ambient desert dust level was associated with an increased risk of allergic symptoms in pollen-sensitized pregnant women when pollen was present in the air. The risk increase was dose dependent and was observed from low levels of desert dust. These results support a hypothesis that ambient desert dust particles exert adjuvant effects in human in real-life settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: UMIN000010826.

Factors associated with the severity of childhood rhinoconjunctivitis.

BACKGROUND: Allergic rhinitis is one of the most common chronic diseases in children. Although it has a large impact on the patient's quality of life, little is known about the factors associated with its severity. The aim of this study was to assess the factors associated with the severity of rhinoconjunctivitis among children in the general population. METHODS: A survey was conducted using an online research panel in 2012. Parents were asked to answer an International Study of Asthma and Allergies in Childhood-based questionnaire to identify children with current rhinoconjunctivitis and evaluate factors associated with the severity of its symptoms. Severity was rated according to the degree of impairment caused by the symptoms in the patient's daily life. RESULTS: Among 26,725 children aged 6-12 years old, rhinoconjunctivitis was defined in 5175 (19.4%), and of these, 688 children (13.3% of children with current rhinoconjunctivitis) presented severe symptoms. Living in areas with a high cedar and cypress pollen count and having concurrent eczema were associated with severe rhinoconjunctivitis [adjusted OR (95% CI): 1.21 (1.00-1.46) and 1.45 (1.20-1.75), respectively]. Further, a maternal history of asthma and allergic rhinitis was a significant risk factor for severe rhinoconjunctivitis [1.34 (1.04-1.74) and 1.30 (1.10-1.53), respectively]. However, living with fur-bearing animals (pets) before 1 year of age proved to be a protective factor against severe rhinoconjunctivitis [0.70 (0.52-0.94)]. CONCLUSIONS: Environmental factors such as pets and pollen, together with comorbidities and a maternal history of allergic diseases, play an important role in determining the severity of rhinoconjunctivitis.

Environmental factors associated with childhood eczema: Findings from a national web-based survey.

BACKGROUND: Genetic and environmental factors are known to be related to the development of childhood eczema. Our aim was to assess the environmental factors associated with the prevalence of eczema among children using a web-based survey. METHODS: In June 2012, we conducted a nation-wide web-based survey to identify the prevalence and characteristics of allergic diseases among Japanese children. The prevalence of allergic diseases including eczema was assessed using the International Study of Asthma and Allergies in Childhood core questionnaire. The associations between eczema prevalence and environmental factors, as well as those between background characteristics and comorbid allergic diseases among 6-12 year old children were assessed. RESULTS: A total of 28,348 children were included in the analysis. The prevalence of current eczema was 13.0%. Current eczema was significantly associated with a higher prevalence of wheeze, rhinitis, and food allergy. In multiple logistic regression models, birth during autumn (aOR: 1.18 95%CI: 1.06-1.31) or winter (aOR: 1.21 95%CI: 1.08-1.34), duration of exclusive breastfeeding for at least 6 months (aOR: 1.14 95%CI: 1.06-1.23), and ownership of a pet from infancy (aOR: 2.61 95%CI: 1.68-4.07) were also associated with a higher prevalence of eczema. The prevalence was lower in those with a high annual household income (aOR: 0.90 95%CI: 0.81-0.99) and 2 or more siblings (aOR: 0.86 95%CI: 0.76-0.97). CONCLUSIONS: Duration of breastfeeding, season of birth, pet ownership, household income, and the number of siblings were associated with the prevalence of childhood eczema in a nationwide web survey.

Factors associated with asthma control in children: findings from a national Web-based survey.

BACKGROUND: Although achieving and maintaining control of asthma is considered to be the goal of asthma treatment, determinants of asthma control are not fully understood. Our aim was to assess factors associated with asthma control among paediatric patients in the general population. METHODS: In June 2012, a Web-based survey was conducted to identify Japanese children aged 6 to 11 yr who currently have asthma and evaluate control of their disease using the Childhood Asthma Control Test (C-ACT). Associations were evaluated among uncontrolled asthma (C-ACT score <20) between environmental factors, demographics and comorbid allergic diseases. RESULTS: Among the 3066 children with current asthma, 447 (14.6%) had uncontrolled asthma. Multivariable analysis identified factors such as low birthweight (adjusted OR 1.65, 95% CI 1.25-2.18), obesity (adjusted OR 1.44, 95% CI 1.05-1.99) and pet ownership before birth (adjusted OR 1.68, 95% CI 1.24-2.29) to be associated with uncontrolled disease. Comorbid allergic diseases, especially rhinitis were a significant risk of uncontrolled asthma (adjusted OR for severe rhinitis: 3.88, 95% CI 2.50-6.00). The severity of rhinitis symptoms was inversely correlated with the C-ACT score (p < 0.001). CONCLUSIONS: A population-based Web survey showed an association between several factors and the control of paediatric asthma. The assessment of these factors may help identify the children at risk with uncontrolled asthma.

Time-dependent variation in the responses to the web-based ISAAC questionnaire.

BACKGROUND: Epidemiologic studies have shown seasonal variations in responses to the written questionnaire for rhinitis symptoms. OBJECTIVE: To evaluate whether the timing of data collection affected responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in a Web-based study. METHODS: The Web-based ISAAC questionnaires were completed by parents with children 6 to 12 years old using an online research system. The authors conducted surveys of asthma symptoms every month for 1 year and surveys of rhinitis and eczema symptoms every season throughout 1 entire year. RESULTS: There was a significant fluctuation in the positive responses to questions about wheezing in the past 12 months (P < .001) but not in the positive responses to questions about exercise-induced wheezing in the past 12 months and asthma ever (P = .75 and P = .15, respectively). The positive responses to questions about rhinitis and allergic rhinoconjunctivitis in the past 12 months and pollinosis ever exhibited significant seasonal variations (P = .002, P < .001, and P < .001, respectively). In contrast, there were no significant variations in positive responses regarding eczema in the past 12 months and eczema ever (P = .33 and P = .55, respectively). CONCLUSION: There were time-dependent fluctuations in responses to the Web-based questionnaire regarding allergic symptoms. Timing of data collection should be taken into account when evaluating prevalence of asthma and rhinitis in children.

A case of mite-ingestion-associated exercise- induced anaphylaxis mimicking wheat-dependent exercise-induced anaphylaxis.

We present a case of mite-ingestion-associated exercise-induced anaphylaxis mimicking wheat-dependent exercise-induced anaphylaxis (WDEIA). A 17-year-old boy was referred for an episode of anaphylaxis while jogging, 1.5 h after having eaten okonomiyaki (a Japanese pancake). Laboratory measures revealed a slightly elevated specific immunoglobulin E (IgE) antibody against omega-5 gliadin (0.41 kUA/l) and a marked elevation of specific IgE antibody against house-dust mite, Dermatophagoides farinae (142 kUA/l). A detailed interview revealed that, in spite of the referring doctor's advice to discontinue postprandial exercises, he continued his jogging routine after consuming foods containing wheat and also that his younger brother, who had mild intermittent asthma, had suffered a mild asthma attack 2 h after eating the same food. We therefore examined the okonimiyaki mix, which had been stored for several months after opening the package until this episode, under a microscope, and we found an abundant number of live mites, D. farinae. Finally, a diagnosis of mite-ingestion-associated exercise-induced anaphylaxis was made. This clinical entity should be excluded when making a diagnosis of WDEIA.

Aerosol characteristics of admixture of budesonide inhalation suspension with a beta2-agonist, procaterol.

BACKGROUND: Nebulized drugs for asthma treatment are often mixed together in order to simplify inhalation regimens, although not recommended. We therefore evaluated aerosol characteristics and physicochemical stability of the admixture of an inhaled corticosteroid suspension with a beta2-agonist solution. METHODS: An 8-stage cascade impactor was used to measure the particle size distribution of admixture of Pulmicort® Respules® (budesonide, 0.5mg/2mL) with Meptin® Inhalation Solution Unit (procaterol hydrochloride, 30µg/0.3mL) from a jet nebulizer, PARI LC Plus®. Concentration of each drug was assayed with high-pressure liquid chromatography. Physicochemical compatibility was also assessed up to 24 hours after mixing. RESULTS: With regard to budesonide, impactor parameters such as mass median aerodynamic diameter (MMAD) and respirable mass (RM) were comparable between admixtures and single-drug preparations (2.92 ± 0.03 vs 2.99 ± 0.14µm, 146.8 ± 2.9 vs 147.6 ± 8.2µg, respectively). On the other hand, delivery rates of procaterol increased when admixed with budesonide suspension, resulting in significantly higher RM (15.1 ± 0.8 vs 10.2 ± 0.5µg, p < 0.01). Variations from initial concentration in the percentages of drug remaining at any time point were less than 10%, and there were no appreciable changes in pH of the admixtures for up to 24 hours. CONCLUSIONS: There is a possibility that admixture might influence of aerodynamic characteristics of procaterol, but not budesonide. In vivo data will be needed for the clinical implications of our findings.